PubMed Health⌕ Search

Biomedical subjects

Eric Klein

Publications and source records attributed to Eric Klein.

13 recordsLinked to original sources
PubMed2005

Novel role of prostate-specific membrane antigen in suppressing prostate cancer invasiveness.

Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein, is overexpressed in prostate cancer. PSMA is a unique cell surface marker, negatively regulated by androgen and extensively used for imaging of hormone refractory carcinomas and metastatic foci. PSMA is a carboxypeptidase with two important enzymatic functions, namely, folate hydrolase and NAALADase. PSMA also exhibits an endocytic function, in which it spontaneously recycles through endocytic vesicles. PSMA is overexpressed at various stages of prostate cancer, including androgen-sensitive and -independent disease, increased in expression with early relapse after therapy. We have used in vitro invasion assays to explore the possible role of PSMA in the metastasis of prostate cancer cells. Androgen-dependent prostate cancer lines, which express PSMA endogenously (e.g., LNCaP, MDA PCa2b, and CWR22Rv1) are less invasive compared with androgen-independent PC3 or DU145 cells, neither of which expresses PSMA. Ectopic expression of PSMA in PC3 cells reduced the invasiveness of these cells, suggesting that this reduction in the invasion capability of PSMA-expressing cells is due to PSMA expression and not to intrinsic properties of different prostate cancer cell lines. Furthermore, knockdown of PSMA expression increased invasiveness of LNCaP cells by 5-fold. Finally, expression of PSMA mutants lacking carboxypeptidase activity reduced the impact of PSMA expression on invasiveness. Thus, it seems that the enzymatic activity is associated with the effect of PSMA on invasiveness.

Antigens, Surface↗
PubMed2005

Prognostic impact of positive surgical margins in surgically treated prostate cancer: multi-institutional assessment of 5831 patients.

OBJECTIVES: To assess the prognostic significance of a positive surgical margin in the radical prostatectomy specimen, and to test for the presence of statistically significant interactions between surgical margin status and select pathologic stage variables. METHODS: We combined prospectively collected data from 7816 consecutive patients treated with radical prostatectomy at eight institutions. The pretreatment serum prostate-specific antigen level, pathologic Gleason sum, surgical margin status (positive versus negative), presence of extracapsular extension, seminal vesicle involvement, and pelvic lymph node status were examined as predictors of the rate of biochemical progression in 5831 patients with complete records. RESULTS: In multivariate Cox regression models, a positive surgical margin was associated with a 3.7-fold greater risk of progression (P = 0.001). Moreover, a statistically significant interaction was found between surgical margin status and Gleason sum 7 to 10 (P = 0.008) and lymph node invasion (P < 0.001). CONCLUSIONS: The presence of a positive surgical margin in the radical prostatectomy specimen has an adverse effect on prognosis. The greatest risk of biochemical recurrence may be expected if a positive surgical margin is present with Gleason sum 7 to 10 disease or lymph node invasion.

Disease-Free Survival↗
PubMed2004

Efficacy and factors associated with successful outcome of sildenafil citrate use for erectile dysfunction after radical prostatectomy.

OBJECTIVES: To assess the efficacy and factors associated with successful treatment of sildenafil citrate for erectile dysfunction after radical prostatectomy (RP). METHODS: Of the 470 patients who underwent RP at our institution between July 1998 and January 2000, 227 (48%) sought treatment for erectile dysfunction, and 174 (37%) were prescribed sildenafil citrate. The starting dose was 50 mg, which was increased to 100 mg if the patient did not have a positive response. Of the 174 patients, 104 (59.8%) had undergone a bilateral nerve-sparing (NS) procedure, 28 (16.1%) had undergone a unilateral NS procedure, and 42 (24.1%) had undergone a non-NS procedure. Erectile function was assessed by the abridged five-item version of the International Index of Erectile Function questionnaire, referred to as the Sexual Health Inventory for Men (SHIM), at baseline and 1 year after sildenafil use. The patients' charts were retrospectively reviewed to find factors associated with a successful outcome, which was defined as successful vaginal intercourse. Association with success was assessed by chi-square analysis and the Cochran Armitage test for trend. Bonferroni correction for multiple comparisons was used, with an overall significance level of 0.05 for each factor assessed. RESULTS: The mean age was 60.1 +/- 6.25 years, and the mean interval from RP to drug use was 3 months. After treatment with sildenafil, 100 (57%) of 174 patients responded to the drug: 79 (76%) of 104 in the bilateral NS group, 15 (53.5%) of 28 in the unilateral NS group, and 6 (14.2%) of 42 in the non-NS group. SHIM analysis showed that the magnitude of the improvement was greater in the bilateral NS group (19.97 +/- 1.12) than in the unilateral NS (15.89 +/- 3.38) or non-NS (10.06 +/- 2.0) groups (P <0.020). Four factors were significantly associated statistically with a successful outcome: the presence of at least one neurovascular bundle, a preoperative SHIM score of 15 or greater, age 65 years old or younger, and interval from RP to drug use of more than 6 months (P <0.001). CONCLUSIONS: The efficacy of sildenafil citrate after RP correlated with the degree of neurovascular bundle preservation, preoperative erectile function status, age, and interval before starting treatment.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

Female sexual dysfunction after radical cystectomy: a new outcome measure.

OBJECTIVES: To assess, in our contemporary radical cystectomy (RC) series, female sexual dysfunction and whether the type of diversion affected the occurrence of sexual dysfunction. Outcome data after RC with and without orthotopic diversion has focused primarily on cure, urethral recurrence, and continence. METHODS: The baseline and follow-up data from 27 sexually active female patients (mean age 54.79 +/- 12.7 years) who underwent RC from 1997 to 2002 for transitional cell carcinoma of the bladder (16 with Stage T1-T2 and 11 with Stage T3-T4) were obtained. Thirteen patients were premenopausal before RC. Of the 27 patients, 10 (37%) underwent Studor orthotopic diversion, 7 (26%) Indiana cutaneous diversion, and 10 (37%) ileal conduit diversion. A 10-item version of the self-administered Index of Female Sexual Function questionnaire was used to assess sexual dysfunction. The specific domains analyzed in the Index of Female Sexual Function include the degree of vaginal lubrication, ability to achieve orgasm, degree of pain during intercourse, overall sexual desire and interest, and overall sexual satisfaction, with responses graded on a scale of 1 (almost never, never) to 5 (almost always, always). RESULTS: With a mean follow-up of 24.2 months (range 15 to 65.1), the total mean baseline Index of Female Sexual Function score decreased from 17.4 +/- 7.23 to 10.6 +/- 6.62 after RC (P < or =0.05). The most common symptoms reported by the patients included diminished ability or inability to achieve orgasm in 12 (45%), decreased lubrication in 11 (41%), decreased sexual desire in 10 (37%), and dyspareunia in 6 patients (22%). Only 13 (48%) of the 27 patients were able to have successful vaginal intercourse, with 14 (52%) reporting decreased satisfaction in overall sexual life after RC. Eight partners (30%) had a decrease in desire for sexual activity owing to apprehension after cancer diagnosis and treatment. Although the numbers were small, the preliminary data suggested no differences in sexual function between patients undergoing Studor orthotopic diversions and those undergoing Indiana cutaneous diversions. CONCLUSIONS: Sexual dysfunction is a prevalent problem after female RC. The nature of the dysfunction involves multiple domains, including decreased orgasm, decreased lubrication, lack of sexual desire, and dyspareunia. Our early results suggest that the type of continent diversion does not affect sexual function. Surgical modifications such as urethral and vaginal sparing, neurovascular preservation, and tubular vaginal reconstruction sparing may improve female sexual function after RC.

Carcinoma, Transitional Cell↗
PubMed2004

Is year of radical prostatectomy a predictor of outcome in prostate cancer?

PURPOSE: We examined whether the year in which radical prostatectomy (RP) was performed is a predictor of treatment outcome after controlling for standard prognostic factors. MATERIALS AND METHODS: We examined the association between RP year and outcome in 6,556 patients from 7 centers using preoperative and pathological features. Patients underwent surgery between 1985 and 2000. The variables analyzed were RP year, clinical stage, pretreatment prostate specific antigen, biopsy Gleason sum, RP Gleason sum, margin status, level of extracapsular extension, seminal vesicle status, lymph node status, neoadjuvant hormones and adjuvant therapy. Median followup was 23 months (maximum 166). Separate Cox multivariate regression analyses were performed to analyze preoperative and postoperative factors. RESULTS: RP year was a predictor of outcome on preoperative analysis (p = 0.006) but not on postoperative analysis (p = 0.130). Patient outcome steadily improved with surgery through the mid 1990s and then it appeared to level off. CONCLUSIONS: When controlling for preoperative features, the year in which RP was performed is a predictor of outcome on multivariate analysis. This effect could not be explained by stage migration.

Adult↗
PubMed2004

Preoperative autologous donation versus cell salvage in the avoidance of allogeneic transfusion in patients undergoing radical retropubic prostatectomy.

UNLABELLED: There are many methods for preventing allogeneic blood administration during radical retropubic prostatectomy, and many of these methods have been compared with each other, but no studies have compared preoperative autologous donation (PAD) and cell salvage (CS). In this study, we evaluated these two methods in patients undergoing radical retropubic prostatectomy. In a prospective cohort model, allogeneic exposure in patients from one surgeon who routinely had his patients donate blood before surgery was compared with that in patients from a different surgeon who predominantly used CS. Fifty patients were enrolled in the study: 26 in the PAD group and 24 in the CS group. No difference in allogeneic exposure was seen between the two groups. A significant difference was seen in the volume of red blood cells lost (891 +/- 298 mL versus 1134 +/- 358 mL in the PAD and CS groups, respectively). We conclude that PAD and CS are equivalent in their ability to avoid allogeneic transfusion. Larger surgical blood loss in the CS group would suggest that in a more rigorously designed study, CS might provide better allogeneic avoidance than PAD. IMPLICATIONS: In this prospective cohort study, cell salvage and preoperative autologous donation were compared with respect to their ability to avoid allogeneic transfusion. There was a suggestion that cell salvage might offer better allogeneic transfusion avoidance.

Aged↗
PubMed2003

Long-term effect of sildenafil citrate on erectile dysfunction after radical prostatectomy: 3-year follow-up.

OBJECTIVES: To evaluate the long-term effect and safety of sildenafil citrate for the treatment of erectile dysfunction after radical prostatectomy (RP). METHODS: The study consisted of 91 patients with erectile dysfunction from our institution who received oral sildenafil citrate after RP. We surveyed these patients using a self-administered questionnaire during the first year of sildenafil citrate use to determine treatment satisfaction, patient compliance, and safety. Those who had responded positively to the drug were surveyed again 3 years later (n = 48). Sildenafil citrate was prescribed at a dose of 50 mg and increased to 100 mg if needed. Data were collected from a self-administered questionnaire using the abridged five-item version of the International Index of Erectile Function questionnaire, referred to as the Sexual Health Inventory of Men, and the Erectile Dysfunction Inventory of Treatment Satisfaction. The patients were stratified according to the type of nerve-sparing (NS) RP procedure they underwent: bilateral NS, unilateral NS, and non-NS. RESULTS: At 3 years, 31 (71%) of the 43 patients who had returned the second surveys were still responding to sildenafil. Of these 31 respondents, 10 (31%) had augmented their dose from 50 to 100 mg. The dropout rate was 27%; 6 of 12 had discontinued because of the return of natural erections, 5 because of a loss of efficacy, and 1 because his spouse had died. No differences were found in the 1-year and 3-year five-item International Index of Erectile Function (Sexual Health Inventory of Men) and Erectile Dysfunction Inventory of Treatment Satisfaction scores between the NS groups. The most common side effects at 3 years were headache (12%), flushing (10%), and blue or blurred vision (2%). No patient discontinued the drug at 3 years because of side effects. CONCLUSIONS: The results of this study indicate that the vast majority of patients with erectile dysfunction after RP who initially respond to sildenafil continue to do so at 3 years and are satisfied and compliant with the treatment regimen.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Long-term potency after iodine-125 radiotherapy for prostate cancer and role of sildenafil citrate.

OBJECTIVES: To assess the long-term sexual potency and attrition in sexual function after iodine-125 ((125)I) seed radiotherapy and the effect of sildenafil on radiation-induced erectile dysfunction (ED). METHODS: This prospective study consisted of 86 sexually active patients (mean age 63.5 +/- 7.7 years) who underwent (125)I seed implantation from 1997 to 1999 to treat low-volume prostate cancer (prostate-specific antigen less than 10 ng/mL, Gleason score 6 or less, stage T1-T2). All patients were followed up every 6 to 8 months for 4 years. Patients prescribed sildenafil citrate for ED completed the abridged five-item version of the International Index of Erectile Function (IIEF) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaires. RESULTS: The median follow-up was 49.7 months (range 36 to 66). Of 86 patients, 43 (50%) did not initiate drug therapy; and only 36 (83.7%) of the 43 were interviewed at 4 years. Twenty-three (63.8%) of the 36 patients had erections sufficient for vaginal penetration, with a total mean +/- SD IIEF-5 score of 15.76 +/- 1.13. The other 50% (43 of 86) initiated sildenafil citrate for treatment of ED after seed implantation, with a minimal follow-up of 6 months. At 4 years, 32 (74%) of the 43 were responding positively to sildenafil citrate, with a total IIEF-5 score of 18.3 +/- 1.2. The mean EDITS +/- SD score was 76.5 +/- 3.2, and the spousal satisfaction rate was 72% (31 of 43). The dropout rate was 37% (16 of 43); 10 (63%) of the 16 discontinued because of a lack of efficacy, 3 (19%) because of a return of natural erections sufficient for vaginal penetration, and 3 (19%) discontinued because of side effects (headaches). CONCLUSIONS: ED is a major long-term issue after (125)I seed radiotherapy, with a long-term potency rate of 29%. Sildenafil citrate improves erections in most patients after (125)I seed implantation.

Adenocarcinoma↗
PubMed2003

A preoperative nomogram identifying decreased risk of positive pelvic lymph nodes in patients with prostate cancer.

PURPOSE: We developed a preoperative nomogram for prediction of lymph node metastases in patients with clinically localized prostate cancer. MATERIALS AND METHODS: The study was a retrospective, nonrandomized analysis of 7,014 patients treated with radical prostatectomy at 6 institutions between 1985 and 2000. Exclusion criteria consisted of preoperative androgen ablation therapy, salvage radical prostatectomy and pretreatment prostate specific antigen (PSA) greater than 50 ng/ml. Preoperative predictors of lymph node metastases consisted of pretreatment PSA, clinical stage (1992 TNM) and biopsy Gleason sum. These predictors were used in logistic regression analysis based nomograms to predict the probability of lymph node metastases. RESULTS: Overall 5,510 patients with complete clinical and pathological information were included in the study. Lymph nodes metastases were present in 206 patients (3.7%). Pretreatment PSA, biopsy Gleason sum, clinical stage and institution represented predictors of lymph node status (p <0.001). Bootstrap corrected predictive accuracy of the 3-variable nomogram (clinical stage, Gleason sum and PSA) was 0.76. Inclusion of a fourth variable, which accounts for institutional differences in lymph node metastases, yielded an area under the receiver operating characteristics curve of 0.78. The negative predictive value of our nomograms was 0.99 when they predicted 3% or less chance of positive lymph nodes. CONCLUSIONS: Using clinical information, we produced 2 calibrated and validated nomograms, which accurately predict pathologically negative lymph nodes in men with localized prostate cancer who are candidates for radical prostatectomy.

Adult↗
PubMed2002

International validation of a preoperative nomogram for prostate cancer recurrence after radical prostatectomy.

PURPOSE: We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents. METHODS: Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification-based risk quadrants were compared with actual Kaplan-Meier plots. RESULTS: The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low-risk group), 39% (intermediate-high-risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram. CONCLUSION: The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.

Adult↗
PubMed2002

Validation study of the accuracy of a postoperative nomogram for recurrence after radical prostatectomy for localized prostate cancer.

PURPOSE: A postoperative nomogram for prostate cancer was developed at Baylor College of Medicine. This nomogram uses readily available clinical and pathologic variables to predict 7-year freedom from recurrence after radical prostatectomy. We evaluated the predictive accuracy of the nomogram when applied to patients of four international institutions. PATIENTS AND METHODS: Clinical and pathologic data of 2,908 patients were supplied for validation, and 2,465 complete records were used. Nomogram-predicted probabilities of 7-year freedom from recurrence were compared with actual follow-up in two ways. First, the area under the receiver operating characteristic curve (AUC) was calculated for all patients and stratified by the time period of surgery. Second, calibration of the nomogram was achieved by comparing the predicted freedom from recurrence with that of an ideal nomogram. For patients in whom the pathologic report does not distinguish between focal and established extracapsular extension (an input variable of the nomogram), two separate calculations were performed assuming one or the other. RESULTS: The overall AUC was 0.80 when applied to the validation data set, with individual institution AUCs ranging from 0.77 to 0.82. The predictive accuracy of the nomogram was apparently higher in patients who were operated on between 1997 and 2000 (AUC, 0.83) compared with those treated between 1987 and 1996 (AUC, 0.78). Nomogram predictions of 7-year freedom from recurrence were within 10% of an ideal nomogram. CONCLUSION: The postoperative Baylor nomogram was accurate when applied at international treatment institutions. Our results suggest that accurate predictions may be expected when using this nomogram across different patient populations.

Adult↗
PubMedDate not supplied

Challenges and opportunities to the design and implementation of chemoprevention trials for prostate cancer.

Since 1991 and the activation of the Prostate Cancer Prevention Trial as well as similar prevention studies in several other organ sites, the interest in prostate cancer prevention has increased substantially. Despite such interest, the challenges to prevention trials-in design, implementation, prioritization, and allocation of resources-are substantial. Simultaneously, there has been an explosion in new targets and agents that may have an effect in the prevention of this disease. In this manuscript, we discuss these challenges to the study of prostate cancer prevention and provide a blueprint for prioritization of future studies.

Adenocarcinoma↗